Analyses of the pathways taken by multipotential progenitor cells in giving rise to diverse elements of the hematopoietic system are poorly understood. The relationship between different pathways of hematopoietic differentiation has been investigated using in vivo transformation of bone marrow cells with retroviruses containing v-myc alone, v-raf alone or the two oncogenes in a single retrovirus construct. Viruses containing the single oncogenes were found to induce only B cell lineage tumors while the dual-oncogene virus induced cell lines with the ability to differentiate along two different pathways, yielding mature macrophages or mature B cells. These results support earlier suggestions of a close relationship between the myeloid and B cell differentiative pathways.